Pathomechanisms of persistent aura

Extrastriate cortex is shown in yellow (Brodmann area 19) and orange (Brodmann area 18). Striate cortex (Brodmann area 17) is shown in red. Quoted from Wikipedia article "Extrastriate cortex" (see here).

The elucidation of the pathomechanisms of persistent aura without infarction is a challenge of the basic neurosciences. As has been pointed out by David C. Haas (1981) in his classical paper on prolonged migraine aura status, "Episodes of migraine aura status have more than clinical importance, for they need to be considered in any hypothesis put forth to explain the mechanism of the migraine aura" (p. 199). Referring to the variety of persistent aura with persistent positive visual phenomena, Liu et al. (1995) speculated that their patients' symptoms (e.g. TV static, snow) may have resulted from spontaneous cortical discharges. "Thus, selective dysfunction of inhibitory and modulating neurons in extrastriate areas may have allowed spontaneous discharges from the lateral geniculate or visual cortex, resulting in the release visual hallucinations as suggested by West and Cogan." (Liu et al., 1995, p. 668) The favourable response to antiseizure drugs reported in some cases of persistent aura (Rothrock, 1997; Chen et al., 2001; Celiker et al., 2007) suggests an ictal process akin to "aura continua", i.e. prolonged episodes of sensory symptoms similar or identical to a seizure aura lasting hours to years, the exact pathophysiology of which clinical phenomenon awaits clarification, too (Seshia and McLachlan, 2005). The presence of a such neurophysiological similarity between migrainous aura and epileptic seizure is supported by observations of "migralepsy", i.e. migraine-triggered epileptic seizures (Barré et al., 2008). Recent findings from genetic and epidemiological studies further support this link.

More recently, as summarized by Agostini and Aliprandi (2006), 10 patients with persistent visual aura symptoms have been studied with advanced MRI perfusion or diffusion imaging techniques or SPECT (for a review of neuroimaging findings in migraine in general see here). In these patients, reduced perfusion of occipital cortex could be demonstrated during the episode of persistent aura, while it returned to normal levels after full remission of symptoms (Relja et al., 2005). The decreased cerebral blood flow, however, must be above the ischemic threshold since a stroke did not develop and no permanent brain lesion could be detected. These findings suggest that localised brain oligaemia plays a major role in the pathogenetic mechanisms responsible for the neurological symptoms of persistent aura. The reason why cerebral oligaemia is sustained in these patients, however, is still not understood. Especially, it is not known whether this persistent cerebral oligaemia may be consequent to cortical spreading depression, the spreading of a self-propagating wave of cellular depolarization in the cerebral cortex which is considered to be involved in the pathomechanisms of the transitory migraine aura (see here).

Bereczki et al. (2008) presented imaging evidence of the spreading of cortical edema with reversibly restricted water diffusion from the left occipital to the temporo-parietal cortex in persistent visual migraine aura in a 58-year-old man. The right-sided visual field defect with a duration of 15 days was associated with discoupling of glucose metabolism and blood flow and the decreased apparent diffusion coefficient also suggested cytotoxic edema. Eight weeks after onset of symptoms no signs were present, and magnetic resonance imaging became normal. The case shows that long-lasting restricted cortical water diffusion, even if coupled with hypometabolism and edema, can be reversible in persistent visual migraine aura.

Schulz et al. (2007) used phosphorus and proton MR-spectroscopy to examine 9 patients with a history of persistent aura without infarction (duration > 7 days) with motor (8 cases, 3 of them also displaying sensory symptoms and 2 with episodes of migrainous coma) or visual and sensory symptoms (1 case) at least 2 weeks after full remission of the last episode, comparing their results with those obtained in 12 patients with migraine with aura (duration ≤ 7 days) and 16 healthy controls with no history of migraine. Abnormal findings were restricted to phosphorus MR-spectroscopy of cerebral grey matter which demonstrated, compared to controls, abnormal energy metabolism in patients with hemiplegic migraine and in patients with persistent aura > 7 days, but not in the other patients. Disturbances in migraine metabolism may determine the clinical manifestations of the aura once an attack has started. The findings support the concept of migraine with aura being a heterogeneous disorder with distinct pathophysiological subtypes, where the pathophysiological mechanisms underlying different migraine subtypes may differ (Eriksen et al., 2006).

References

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Schulz UG, Blamire AM, Corkill RG, Davies P, Styles P, Rothwell PM. Association between cortical metabolite levels and clinical manifestations of migrainous aura: an MR-spectroscopy study. Brain 2007; 130: 3102-3110.
West LJ. A general theory of hallucinations and dreams. In: West LJ (ed) Hallucinations. Grune & Stratton, New York 1962, pp. 275-291.

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